Chemically modified siRNA: tools and applications

Drug Discovery Today

Volumn 13, Issue 19-20, 2008, Pages 842-855

  Watts, Jonathan K ^a   Deleavey, Glen F ^a   Damha, Masad J ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

4 THIOURACIL; AGN 745; AKI I5; ALN RSV01; BEVASIRANIB; CALAA 01; DIHYDROURACIL; FOMIVIRSEN; NANOPARTICLE; NUCLEASE; PEGAPTANIB; PHOSPHOROTHIOIC ACID; PYRIMIDINE; RTP 801I 14; SHORT HAIRPIN RNA; SMALL INTERFERING RNA; TD 101; UNCLASSIFIED DRUG;

ACUTE KIDNEY FAILURE; CHEMICAL MODIFICATION; CONGENITAL PACHYONYCHIA; DRUG DELIVERY SYSTEM; DRUG POTENCY; ENZYME STABILITY; HYBRIDIZATION; IMMUNOREACTIVITY; NEOPLASM; PROTEIN INDUCTION; RETINA MACULA DEGENERATION; REVIEW; RNA STRUCTURE; SENSITIVITY AND SPECIFICITY;

ANIMALS; DRUG DELIVERY SYSTEMS; HUMANS; NUCLEIC ACID HYBRIDIZATION; NUCLEOTIDES; RNA, SMALL INTERFERING;

EID: 52049090811     PISSN: 13596446     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.drudis.2008.05.007     Document Type: Review

References (138)

1. Fire A., et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391 (1998) 806-811
2. Elbashir S.M., et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411 (2001) 494-498
3. Rana T.M. Illuminating the silence: understanding the structure and function of small RNAs. Nat. Rev. Mol. Cell Biol. 8 (2007) 23-36
4. Tomari Y., and Zamore P.D. Perspective: machines for RNAi. Genes Dev. 19 (2005) 517-529
5. Grünweller A., and Hartmann R.K. RNA interference as a gene-specific approach for molecular medicine. Curr. Med. Chem. 12 (2005) 3143-3161
6. Schwarz D.S., et al. Asymmetry in the assembly of the RNAi enzyme complex. Cell 115 (2003) 199-208
7. Khvorova A., et al. Functional siRNAs and miRNAs exhibit strand bias. Cell 115 (2003) 209-216
8. Hamada M., et al. Effects on RNA interference in gene expression (RNAi) in cultured mammalian cells of mismatches and the introduction of chemical modifications at the 3′-ends of siRNAs. Antisense Nucl. Acid Drug Dev. 12 (2002) 301-309
9. Parrish S., et al. Functional anatomy of a dsRNA trigger: differential requirement for the two trigger strands in RNA interference. Mol. Cell 6 (2000) 1077-1087
10. Soutschek J., et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432 (2004) 173-178
11. Kraynack B.A., and Baker B.F. Small interfering RNAs containing full 2′-O-methylribonucleotide-modified sense strands display Argonaute2/eIF2C2-dependent activity. RNA 12 (2006) 163-176
12. Ui-Tei K., et al. Functional dissection of siRNA sequence by systematic DNA substitution: modified siRNA with a DNA seed arm is a powerful tool for mammalian gene silencing with significantly reduced off-target effect. Nucl. Acids Res. 36 (2008) 2136-2151
13. Chiu Y.L., and Rana T.M. siRNA function in RNAi: a chemical modification analysis. RNA 9 (2003) 1034-1048
14. Braasch D.A., et al. RNA interference in mammalian cells by chemically-modified RNA. Biochemistry 42 (2003) 7967-7975
15. Elbashir S.M., et al. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J 20 (2001) 6877-6888
16. Czauderna F., et al. Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells. Nucl. Acids Res. 31 (2003) 2705-2716
17. Choung S., et al. Chemical modification of siRNAs to improve serum stability without loss of efficacy. Biochem. Biophys. Res. Commun. 342 (2006) 919-927
18. Davis S., et al. Improved targeting of miRNA with antisense oligonucleotides. Nucl. Acids Res. 34 (2006) 2294-2304
19. Dorn G., et al. siRNA relieves chronic neuropathic pain. Nucl. Acids Res. 32 (2004) e49
20. Prakash T.P., et al. Positional effect of chemical modifications on short interference RNA activity in mammalian cells. J. Med. Chem. 48 (2005) 4247-4253
21. Amarzguioui M., et al. Tolerance for mutations and chemical modifications in a siRNA. Nucl. Acids Res. 31 (2003) 589-595
22. Chen X.L., et al. Poly-2′-DNP-RNAs with enhanced efficacy for inhibiting cancer cell growth. Oligonucleotides 14 (2004) 90-99
23. Harborth J., et al. Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. Antisense Nucl. Acid Drug Dev. 13 (2003) 83-105
24. Blidner R.A., et al. Fully 2′-deoxy-2′-fluoro substituted nucleic acids induce RNA interference in mammalian cell culture. Chem. Biol. Drug Des. 70 (2007) 113-122
25. Layzer J.M., et al. In vivo activity of nuclease-resistant siRNAs. RNA 10 (2004) 766-771
26. Damha M.J., et al. Hybrids of RNA and arabinonucleic acids (ANA and 2′F-ANA) are substrates of Ribonuclease H. J. Am. Chem. Soc. 120 (1998) 12976-12977
27. Wilds C.J., and Damha M.J. 2′-Deoxy-2′-fluoro-β-d-arabinonucleosides and oligonucleotides (2′F-ANA): synthesis and physicochemical studies. Nucl. Acids Res. 28 (2000) 3625-3635
28. Dowler T., et al. Improvements in siRNA properties mediated by 2′-deoxy-2′-fluoro-β-d-arabinonucleic acid (FANA). Nucl. Acids Res. 34 (2006) 1669-1675
29. Watts J.K., et al. 2′-Fluoro-4′-thioarabino-modified oligonucleotides: conformational switches linked to siRNA activity. Nucl. Acids Res. 35 (2007) 1441-1451
30. Hoshika S., et al. RNA interference induced by siRNAs modified with 4′-thioribonucleosides in cultured mammalian cells. FEBS Lett. 579 (2005) 3115-3118
31. Dande P., et al. Improving RNA interference in mammalian cells by 4′-thio-modified small interfering RNA (siRNA): effect on siRNA activity and nuclease stability when used in combination with 2′-O-alkyl modifications. J. Med. Chem. 49 (2006) 1624-1634
32. Hoshika S., et al. Study of modification pattern-RNAi activity relationships by using siRNAs modified with 4′-thioribonucleosides. ChemBioChem 8 (2007) 2133-2138
33. Petersen M., and Wengel J. LNA: a versatile tool for therapeutics and genomics. Trends Biotechnol. 21 (2003) 74-81
34. Elmen J., et al. Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucl. Acids Res. 33 (2005) 439-447
35. Bramsen J.B., et al. Improved silencing properties using small internally segmented interfering RNAs. Nucl. Acids Res. 35 (2007) 5886-5897
36. Mook O.R., et al. Evaluation of locked nucleic acid-modified small interfering RNA in vitro and in vivo. Mol. Cancer Therap. 6 (2007) 833-843
37. Hornung V., et al. Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat. Med. 11 (2005) 263-270
38. Hall A.H.S., et al. RNA interference using boranophosphate siRNAs: structure-activity relationships. Nucl. Acids Res. 32 (2004) 5991-6000
39. 2+-dependent endonuclease. Curr. Biol. 14 (2004) 787-791
40. Braasch D.A., et al. Biodistribution of phosphodiester and phosphorothioate siRNA. Bioorg. Med. Chem. Lett. 14 (2004) 1139-1143
41. Prakash T.P., et al. RNA interference by 2′,5′-linked nucleic acid duplexes in mammalian cells. Bioorg. Med. Chem. Lett. 16 (2006) 3238-3240
42. Iwase R., et al. Solid-phase synthesis of modified RNAs containing amide-linked oligoribonucleosides at their 3′-end and their application to siRNA. Nucleosides Nucleotides Nucl. Acids 26 (2007) 1451-1454
43. Sipa K., et al. Effect of base modifications on structure, thermodynamic stability, and gene silencing activity of short interfering RNA. RNA 13 (2007) 1301-1316
44. Hornung V., et al. 5′-Triphosphate RNA is the ligand for RIG-I. Science 314 (2006) 994-997
45. Xia J., et al. Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide. ACS Chem. Biol. 1 (2006) 176-183
46. Holen T., et al. Positional effects of short interfering RNAs targeting the human coagulation trigger tissue factor. Nucl. Acids Res. 30 (2002) 1757-1766
47. Marques J.T., et al. A structural basis for discriminating between self and nonself double-stranded RNAs in mammalian cells. Nat. Biotechnol. 24 (2006) 559-565
48. Nykanen A., et al. ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell 107 (2001) 309-321
49. Chen P.Y., et al. Strand-specific 5′-O-methylation of siRNA duplexes controls guide strand selection and targeting specificity. RNA 14 (2008) 263-274
50. Morrissey D.V., et al. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat. Biotechnol. 23 (2005) 1002-1007
51. Morrissey D.V., et al. Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication. Hepatology 41 (2005) 1349-1356
52. Chiu Y.-L., and Rana T.M. RNAi in human cells: basic structural and functional features of small interfering RNA. Mol. Cell 10 (2002) 549-561
53. Muratovska A., and Eccles M.R. Conjugate for efficient delivery of short interfering RNA (siRNA) into mammalian cells. FEBS Lett. 558 (2004) 63-68
54. Lorenz C., et al. Steroid and lipid conjugates of siRNAs to enhance cellular uptake and gene silencing in liver cells. Bioorg. Med. Chem. Lett. 14 (2004) 4975-4977
55. Bolcato-Bellemin A.-L., et al. Sticky overhangs enhance siRNA-mediated gene silencing. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 16050-16055
56. Martinez J., et al. Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell 110 (2002) 563-574
57. Schwarz D.S., et al. Evidence that siRNAs function as guides, not primers, in the Drosophila and human RNAi pathways. Mol. Cell 10 (2002) 537-548
58. Siolas D., et al. Synthetic shRNAs as potent RNAi triggers. Nat. Biotechnol. 23 (2005) 227-231
59. Brummelkamp T.R., et al. A system for stable expression of short interfering RNAs in mammalian cells. Science 296 (2002) 550-553
60. Banan N., and Puri M. The ins and outs of RNAi in mammalian cells. Curr. Pharm. Biotechnol. 5 (2004) 441-450
61. Abe N., et al. Dumbbell-shaped nanocircular RNAs for RNA interference. J. Am. Chem. Soc. 129 (2007) 15108-15109
62. Holen T., et al. Similar behaviour of single-strand and double-strand siRNAs suggests they act through a common RNAi pathway. Nucl. Acids Res. 31 (2003) 2401-2407
63. Kim D.-H., et al. Synthetic dsRNA dicer substrates enhance RNAi potency and efficacy. Nat. Biotechnol. 23 (2005) 222-226
64. Minks M.A., et al. Structural requirements of double-stranded RNA for the activation of 2′,5′-Oligo(A) polymerase and protein kinase of interferon-treated HeLa-cells. J. Biol. Chem. 254 (1979) 180-183
65. Kennedy S., et al. A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans. Nature 427 (2004) 645-649
66. Takabatake Y., et al. Chemically modified siRNA prolonged RNA interference in renal disease. Biochem. Biophys. Res. Commun. 363 (2007) 432-437
67. Allerson C.R., et al. Fully 2′-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA. J. Med. Chem. 48 (2005) 901-904
68. Turner J.J., et al. MALDI-TOF mass spectral analysis of siRNA degradation in serum confirms an RNAse A-like activity. Mol. BioSyst. 3 (2007) 43-50
69. de Fougerolles A., et al. Interfering with disease: a progress report on siRNA-based therapeutics. Nat. Rev. Drug Discov. 6 (2007) 443-453
70. Manoharan, M. (2006) RNA interference and chemical modifications: conformational and stereochemical aspects. Abstracts of Papers, 231st ACS National Meeting, Atlanta, USA, March 26-30
71. Koller E., et al. Competition for RISC binding predicts in vitro potency of siRNA. Nucl. Acids Res. 34 (2006) 4467-4476
72. Schlee M., et al. siRNA and isRNA: two edges of one sword. Mol. Ther. 14 (2006) 463-470
73. Marques J.T., and Williams B.R.G. Activation of the mammalian immune system by siRNAs. Nat. Biotechnol. 23 (2005) 1399-1405
74. Judge A.D., et al. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat. Biotechnol. 23 (2005) 457-462
75. Kim D.-H., et al. Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase. Nat. Biotechnol. 22 (2004) 321-325
76. Reynolds A., et al. Induction of the interferon response by siRNA is cell type- and duplex length-dependent. RNA 12 (2006) 988-993
77. Kleinman M.E., et al. Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature 452 (2008) 591-597
78. Takeda K., and Akira S. Toll-like receptors in innate immunity. Int. Immunol. 17 (2005) 1-14
79. Judge A., and MacLachlan I. Overcoming the innate immune response to small interfering RNA. Hum. Gene Ther. 19 (2008) 111-124
80. Zamanian-Daryoush M., et al. Determinants of cytokine induction by small interfering RNA in human peripheral blood mononuclear cells. J. Interferon Cytokine Res. 28 (2008) 221-233
81. Diebold S.S., et al. Nucleic acid agonists for Toll-like receptor 7 are defined by the presence of uridine ribonucleotides. Eur. J. Immunol. 36 (2006) 3256-3267
82. Judge A.D., et al. Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo. Mol. Ther. 13 (2006) 494-505
83. Cekaite L., et al. Gene expression analysis in blood cells in response to unmodified and 2′-modified siRNAs reveals TLR-dependent and independent effects. J. Mol. Biol. 365 (2007) 90-108
84. Robbins M., et al. 2′-O-Methyl-modified RNAs act as TLR7 antagonists. Mol. Ther. 15 (2007) 1663-1669
85. Karikó K., et al. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23 (2005) 165-175
86. Jackson A.L., et al. Expression profiling reveals off-target gene regulation by RNAi. Nat. Biotechnol. 21 (2003) 635-637
87. Jackson A.L., et al. Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. RNA 12 (2006) 1179-1187
88. Birmingham A., et al. 3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat. Methods 3 (2006) 199-204
89. Zeng Y., et al. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 9779-9784
90. Doench J.G., et al. siRNAs can function as miRNAs. Genes Dev. 17 (2003) 438-442
91. Lim L.P., et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433 (2005) 769-773
92. Fedorov Y., et al. Off-target effects by siRNA can induce toxic phenotype. RNA 12 (2006) 1188-1196
93. Jackson A.L., et al. Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. RNA 12 (2006) 1197-1205
94. Gilmore I.R., et al. The design and exogenous delivery of siRNA for post-transcriptional gene silencing. J. Drug Target. 12 (2004) 315-340
95. Palliser D., et al. An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. Nature 439 (2006) 89-94
96. Xie F.Y., et al. Harnessing in vivo siRNA delivery for drug discovery and therapeutic development. Drug Discov. Today 11 (2006) 67-73
97. Aigner A. Applications of RNA interference: current state and prospects for siRNA-based strategies in vivo. Appl. Microbiol. Biotechnol. 76 (2007) 9-21
98. De Paula D., et al. Hydrophobization and bioconjugation for enhanced siRNA delivery and targeting. RNA 13 (2007) 431-456
99. Ikeda Y., and Taira K. Ligand-targeted delivery of therapeutic siRNA. Pharm. Res. 23 (2006) 1631-1640
100. Wolfrum C., et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat. Biotechnol. 25 (2007) 1149-1157
101. Moschos S.A., et al. Lung delivery studies using siRNA conjugated to TAT(48-60) and penetratin reveal peptide induced reduction in gene expression and induction of innate immunity. Bioconjugate Chem. 18 (2007) 1450-1459
102. McNamara J.O., et al. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat. Biotechnol. 24 (2006) 1005-1015
103. Chu T.C., et al. Aptamer mediated siRNA delivery. Nucl. Acids Res. 34 (2006) e73
104. Zimmermann T.S., et al. RNAi-mediated gene silencing in non-human primates. Nature 441 (2006) 111-114
105. Li W., and Szoka Jr. F.C. Lipid-based nanoparticles for nucleic acid delivery. Pharm. Res. 24 (2007) 438-449
106. Akinc A., et al. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat. Biotechnol. 26 (2008) 561-569
107. Howard K.A., et al. RNA interference in vitro and in vivo using a chitosan/siRNA nanoparticle system. Mol. Ther. 14 (2006) 476-484
108. Zhou J., et al. PAMAM dendrimers for efficient siRNA delivery and potent gene silencing. Chem. Commun. 2006 (2006) 2362-2364
109. Urban-Klein B., et al. RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo. Gene Ther. 12 (2005) 461-466
110. Baigude H., et al. Design and creation of new nanomaterials for therapeutic RNAi. ACS Chem. Biol. 2 (2007) 237-241
111. Minakuchi Y., et al. Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo. Nucl. Acids Res. 32 (2004) e109
112. Takeshita F., et al. Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 12177-12182
113. Heidel J.D., et al. Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 5715-5721
114. Hu-Lieskovan S., et al. Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing's Sarcoma. Cancer Res. 65 (2005) 8984-8992
115. Heyes J., et al. Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids. J. Control. Rel. 107 (2005) 276-287
116. Geisbert T.W., et al. Postexposure protection of guinea pigs against a lethal Ebola virus challenge is conferred by RNA interference. J. Infect. Dis. 193 (2006) 1650-1657
117. Song E., et al. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat. Biotechnol. 23 (2005) 709-717
118. Sato Y., et al. Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nat. Biotechnol. 26 (2008) 431-442
119. Zhang K., et al. Receptor-mediated delivery of siRNAs by tethered nucleic acid base-paired interactions. RNA 14 (2008) 577-583
120. Peer D., et al. Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target. Science 319 (2008) 627-630
121. Oishi M., et al. Lactosylated poly(ethylene glycol)-siRNA conjugate through acid-labile β-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells. J. Am. Chem. Soc. 127 (2005) 1624-1625
122. Shah S., et al. Light-activated RNA interference. Angew. Chem. Int. Ed. 44 (2005) 1328-1332
123. Nguyen Q.N., et al. Light controllable siRNAs regulate gene suppression and phenotypes in cells. BBA Biomembranes 1758 (2006) 394-403
124. Shah S., and Friedman S.H. Tolerance of RNA interference toward modifications of the 5′ antisense phosphate of small interfering RNA. Oligonucleotides 17 (2007) 35-43
125. Mikat V., and Heckel A. Light-dependent RNA interference with nucleobase-caged siRNAs. RNA 13 (2007) 2341-2347
126. Haussecker D. The business of RNAi therapeutics. Hum. Gene Ther. 19 (2008) 451-462
127. de Fougerolles A.R. Delivery vehicles for small interfering RNA in vivo. Hum. Gene Ther. 19 (2008) 125-132
128. Boese Q., et al. Mechanistic insights aid computational short interfering RNA design. Methods Enzymol. 392 (2005) 73-96
129. Huesken D., et al. Design of a genome-wide siRNA library using an artificial neural network. Nat. Biotechnol. 23 (2005) 995-1001
130. Yuan B., et al. siRNA selection server: an automated siRNA oligonucleotide prediction server. Nucl. Acids Res. 32 (2004) W130-W134
131. nd edn (2007), CRC Press 437-464
132. In: Appasani K. (Ed). RNA Interference Technology: From Basic Science to Drug Development (2005), Cambridge University Press
133. Schepers U. RNA Interference in Practice: Principles, Basics and Methods for Gene Silencing in C. elegans, Drosophila, and Mammals (2005), Wiley-VCH
134. In: Sohail M. (Ed). Gene Silencing by RNA Interference: Technology and Application (2005), CRC Press
135. In: Hannon G.J. (Ed). RNAi: A Guide to Gene Silencing (2003), Cold Spring Harbor Press
136. Manoharan M. RNA interference and chemically modified small interfering RNAs. Curr. Opin. Chem. Biol. 8 (2004) 570-579
137. Corey D.R. Chemical modification: the key to clinical application of RNA interference?. J. Clin. Invest. 117 (2007) 3615-3622
138. Akhtar S., and Benter I.F. Nonviral delivery of synthetic siRNAs in vivo. J. Clin. Invest. 117 (2007) 3623-3632